CD5−NK1.1+ γδ T Cells that Develop in a Bcl11b-Independent Manner Participate in Early Protection against Infection

• Published in: Cell reports (Cambridge) Vol. 21; no. 5; pp. 1191 - 1202
• Main Authors: Hatano, Shinya, Murakami, Tesshin, Noguchi, Naoto, Yamada, Hisakata, Yoshikai, Yasunobu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.10.2017; Elsevier
• Subjects: Animals; Antigens, Ly - metabolism; bacteria; Bcl11b; CD5 Antigens - deficiency; CD5 Antigens - genetics; Cells, Cultured; DN2a; Female; Gene Expression; Granzyme; Granzymes - metabolism; host defense; IFN-γ; IL-17A; innate immunity; Interferon-gamma - analysis; Interferon-gamma - metabolism; Interleukin-17 - analysis; Interleukin-17 - metabolism; Listeria monocytogenes; Listeria monocytogenes - physiology; Listeriosis - immunology; Listeriosis - prevention & control; Liver - immunology; Liver - metabolism; Liver - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; NK Cell Lectin-Like Receptor Subfamily B - metabolism; Phenotype; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Repressor Proteins - deficiency; Repressor Proteins - genetics; Repressor Proteins - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism; Tumor Suppressor Proteins - deficiency; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; γδ T cell; γδ T cell; IFN-γ; Bcl11b; innate immunity; IL-17A; bacteria; host defense; Granzyme; Listeria monocytogenes; DN2a
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.10.007

We recently found that a unique subset of innate-like γδ T cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these Bcl11b-independent γδ T cells in the periphery as CD5−NK1.1+ and Granzyme B+, and we show that they are capable of producing interferon (IFN)-γ upon T cell receptor stimulation without Ca2+ influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues, such as the liver. Bcl11b-independent CD5−NK1.1+ γδ T cells appeared and contributed to early protection before Bcl11b-dependent CD5+NK1.1− γδ T cells following Listeria monocytogenes infection, resembling their sequential appearance during development in the thymus. [Display omitted] •CD5−NK1.1+ γδ T cells develop from DN2a thymocytes independently of Bcl11b•CD5−NK1.1+ γδ T cells are IFN-γ+ Granzyme B+ and abundant in the liver of young mice•CD5−NK1.1+ γδ T cells contribute to early protection against Listeria infection•Appearance of γδ T cells in host defense resembles that in thymic development Bcl11b is essential for transition from the DN2a to the DN2b stage in the thymus. Hatano et al. find that CD5−NK1.1+ γδ T cells develop from the DN2a stage in a Bcl11b-independent manner and participate in host defense at an early stage after bacterial infection in periphery.